Surfactant protein B propeptide contains a saposin-like protein domain with antimicrobial activity at low pH.

Surfactant protein B (SP-B) proprotein contains three saposin-like protein (SAPLIP) domains: a SAPLIP domain corresponding to the mature SP-B peptide is essential for lung function and postnatal survival; the function of SAPLIP domains in the N-terminal (SP-B-N) and C-terminal regions of the proprotein is not known. In the current study, SP-B-N was detected in the supernatant of mouse bronchoalveolar lavage fluid (BALF) and in nonciliated bronchiolar cells, alveolar type II epithelial cells, and alveolar macrophages. rSP-B-N indirectly promoted the uptake of bacteria by macrophage cell lines and directly killed bacteria at acidic pH, consistent with a lysosomal, antimicrobial function. Native SP-B-N isolated from BALF also killed bacteria but only at acidic pH; the bactericidal activity of BALF at acidic pH was completely blocked by SP-B-N Ab. Transgenic mice overexpressing SP-B-N and mature SP-B peptide had significantly decreased bacterial burden and increased survival following intranasal inoculation with bacteria. These findings support the hypothesis that SP-B-N contributes to innate host defense of the lung by supplementing the nonoxidant antimicrobial defenses of alveolar macrophages. The Journal of Immunology, 2010, 184: 975-983.